Abstract: SA-PO298

Serelaxin Improves Cardiac and Renal Function in a DOCA-Salt Model of Cardiorenal Syndrome in Rats

Session Information

Category: Cell Biology

  • 204 Extracellular Matrix Biology, Fibrosis, Cell Adhesion

Authors

  • Wang, Dong, Uc denver, Aurora, Colorado, United States
  • Luo, Yuhuan, University of Colorado, Aurora, Colorado, United States
  • Myakala, Komuraiah, University of Colorado, Aurora, Colorado, United States
  • Wang, Xiaoxin, University of Colorado Denver, Aurora, Colorado, United States
  • Orlicky, David J., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Dobrinskikh, Evgenia, University of Colorado, Denver, Aurora, Colorado, United States
  • Levi, Moshe, University of Colorado Denver, Aurora, Colorado, United States
Background

Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats.

Methods

Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks.

Results


Treatment with serelaxin prevented cardiac and renal dysfunction in DOCA-salt rats. Serelaxin prevented cardiac and renal fibrosis, as determined by Picrosirius Red staining and Second Harmonic Generation (SHG) Microscopy. Treatment of DOCA-salt rats with serelaxin decreased renal inflammation, including the expression of TGF-β, NFκB, MCP-1, interleukin-1, interleukin-6, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and CD68 macrophages. Serelaxin also decreased lipid accumulation in kidney in part by decreasing SREBP-1c, SREBP-2, ChREBP, FATP1, HMGCoAR, and LDL receptor, that mediate fatty acid and cholesterol synthesis and uptake, and increasing Acox1 and ABCA1, that mediate fatty acid oxidation and cholesterol efflux.

Conclusion


In conclusion, serelaxin reversed DOCA-salt induced cardiac and renal dysfunction by modulating inflammation, lipid metabolism, and fibrosis.

Funding

  • NIDDK Support